In the following discussion certain articles and methods will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and methods referenced herein do not constitute prior art under the applicable statutory provisions.
According to the American Diabetes Association, diabetes is the fifth-deadliest disease in the United States and kills more than 213,000 people a year, the total economic cost of diabetes in 2002 was estimated at over $132 billion dollars, and the risk of developing type I juvenile diabetes is higher than virtually all other chronic childhood diseases.
A critical component in managing diabetes is frequent blood glucose monitoring. Currently, a number of systems exist for self-monitoring by the patient. One such system may be termed a photometric system or method. In such systems, the first step is to obtain the sample of aqueous fluid containing an analyte to be assayed, usually whole blood or fractions thereof. The sample of blood may be obtained by a finger stick or other means.
The fluid sample is then contacted with an assay pad or membrane. Contact is generally achieved by moving the assay pad or membrane into contact with the liquid sample on the surface of the patient's skin. Following application to the pad or membrane, the target analyte present in the sample passes through the assay pad or membrane by capillary, wicking, gravity flow and/or diffusion mechanisms. Chemical reagents present in the pad or membrane react with the target analyte producing a light absorbing reaction product, or color change.
The assay pad or membrane is then inserted into a monitor where an optical measurement is then made of this color change. In those embodiments where the optical measurement is a reflectance measurement, a surface of the assay pad or membrane is illuminated with a light source. Light is reflected from the surface of the assay pad or membrane as diffuse reflected light. This diffuse light is collected and measured, for example by the detector of a reflectance spectrophotometer. The amount of reflected light is then related to the amount of analyte in the sample; usually the amount of light reflected off the surface of the assay pad or membrane is an inverse function of the amount of analyte contained in the sample.
An algorithm is employed to determine analyte concentration contained in the sample based on the information provided by the detector. Representative algorithms that may be employed where the analyte of interest is glucose and the fluid sample is whole blood are disclosed, for example, in U.S. Pat. Nos. 5,049,487; 5,059,394; 5,843,692 and 5,968,760; the disclosures of which are incorporated herein by reference.
Glucose monitoring technology that relies on the photometric method of quantifying the glucose concentration in whole blood may be subject to errors associated with variations in hematocrit level, or concentration of red blood cells within the blood sample. Various methods have been employed to ensure the accuracy and repeatability of measured glucose concentration using the photometric method across a typical range of hematocrit levels. A normal hematocrit level is 42-54% for men and 36-48% for women. Overall, the normal range is from 36-54%, but for a variety of reasons, those who regularly test their glucose concentrations may have hematocrit levels even lower (anemia) or higher (polycythemia) than these normal ranges. This presents a challenge for the development of accurate glucose monitoring. This is because the meter is typically designed or calibrated assuming the sample will contain a hematocrit level somewhere in the normal range. Diabetics and clinicians make critical medical decisions in the management of their disease based on the readings provided by these meters. Thus, it would be advantageous to have a photometric quantification method that is more accurate across a broader range of hematocrit levels.
Additionally, glucose monitors typically require that the user supply a sufficient quantity of whole blood for an accurate reading. This volume has been around 10 microliters or more in the past, but with the development of newer quantification technologies, the minimum volume has been brought to as low as 1 microliter for photometric meters. This has reduced the burden on diabetics in their testing by reducing the depth of the lancing and the effort to milk a relatively large amount of blood from their lancing site. Again, the calibration of the meter is developed with the assumption that this minimum supply has been delivered to the test strip. If the user has not supplied a sufficient amount, then the meter generally displays an error code and the user must test again. Further, a user may supply more than the typical amount of blood to the test strip, which may lead to an inaccurate result if the calibration of the strip is volume sensitive. It would be advantageous for a photometric meter to have the ability to evaluate and adjust its internal calibration by detecting the amount of fluid supplied to the reagent strip, and applying an appropriate calibration parameter specifically chosen for that volume.
The development of a fully integrated glucose meter system requires incorporating the processes of skin lancing, transfer of blood to the reagent test strip, and quantification of whole blood glucose all in a single device. Such systems may not require any user intervention at all during the quantification process as long as sufficient sample volume is obtained. An automated catalyst, such as heat, vacuum, or pressure may be utilized to obtain a sample of body fluid, or whole blood.
One such device relies on the application of a specific magnitude and duration of a partial vacuum to the skin in order to facilitate the acquisition of a minimum required sample volume. For some individuals, this pre-programmed amount or duration of vacuum may be appropriate. For others, this pre-programmed catalyst may produce either an insufficient or excessive amount of blood, as well as other undesired outcomes, such as excessive bruising (for those with fragile capillary networks), an unnecessary delay in obtaining results (for fast bleeding individuals), as well as excessive residual blood left on the skin. Thus, it would be advantageous if the sample quantification detector could also determine in real-time whether or not a sufficient sample volume has been obtained for an accurate reading, and provide this information as feedback to control the magnitude and/or duration of a catalyst. This feedback driven control would be a significant advantage for integrated glucose monitoring technology.
Photometric assay pads or membranes for analyte concentration measurements typically produce a circular or linear spot when the chemical reagents contained therein react with a fluid containing a specific analyte, such as glucose, within whole blood. An ideal spot may be defined as one in which the color across the spot is uniform and indicative of the concentration of the analyte. A spot which is not ideal may be manifest in one or more of the following ways: non-uniformity of the primary color (e.g., variations in the intensity of blue); presence of non-primary color, such as red, which may be associated with the presence and/or lysis of blood cells, and the above color variations may be distributed randomly or non-uniformly across the spot.
For a variety of reasons, the quality of a spot developed as a result of an analyte reacting with the reagent membrane may not be ideal as described above. Such reasons may include one or more of: flaws or manufacturing variations in the membrane structure; variations in the concentration of the reagent enzyme; mishandling of the membrane during manufacturing; and unintended chemical reactions between the fluid and/or analyte and the reagent structure and/or membrane chemistry (such as another medical drug within the blood sample reacting with the reagent enzyme).
Most devices on the market cannot detect or correct for low quality spots. Their sensors, typically one or more photodiodes, do not have the ability to discretely analyze the flaws within a reagent spot. Thus, there exists a risk that these systems may not provide an accurate reading in circumstances of a non-ideal spot.